Memory formation and retrieval of neuronal silencing in the auditory cortex.

Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan; h-nomu@umin.ac.jp.

2

Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan;

3

Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan; Center for Information and Neural Networks, National Institute of Information and Communications Technology, Osaka 565-0871, Japan.

Abstract

Sensory stimuli not only activate specific populations of cortical neurons but can also silence other populations. However, it remains unclear whether neuronal silencing per se leads to memory formation and behavioral expression. Here we show that mice can report optogenetic inactivation of auditory neuron ensembles by exhibiting fear responses or seeking a reward. Mice receiving pairings of footshock and silencing of a neuronal ensemble exhibited a fear response selectively to the subsequent silencing of the same ensemble. The valence of the neuronal silencing was preserved for at least 30 d and was susceptible to extinction training. When we silenced an ensemble in one side of auditory cortex for conditioning, silencing of an ensemble in another side induced no fear response. We also found that mice can find a reward based on the presence or absence of the silencing. Neuronal silencing was stored as working memory. Taken together, we propose that neuronal silencing without explicit activation in the cerebral cortex is enough to elicit a cognitive behavior.

Freezing time of Arch/paired mice over light ON period. Freezing time during five CS periods was averaged. (A) Freezing time during the whole CS period. (B) Freezing time during 5 s from the start of CS. Error bars indicate mean ± SEM.

Silencing of a small subset of neurons is sufficient to produce and retrieve fear memory. (A) Arch-EYFP expression in a small number of auditory cortical neurons. (B) Behavioral procedure for C and D. (C) Mice showed freezing behavior in response to light delivery to the conditioned, but not the unconditioned side. Each plot denotes the averaged value during light ON epochs (n = 12, *P = 0.033, t11 = 2.4, paired t test). (D) Relationship between the freezing time in response to light delivery on the conditioned side and the proportion of mCherry+ neurons in that area.